1. Field of the Invention
The present invention relates to a new process for producing 1-phthalidyl-5-fluorouracil derivatives which comprises reacting phthalidylammonium derivatives with 5-fluorouracil (hereinafter abbreviated as to 5-FU). The compounds of the present invention are known to have potent antitumor activity and can be utilized as antitumor agents for humans and animals, and they are particularly useful in treatment of various malignant tumors.
2. Description of the Prior Art
The 1-phthalidyl-5-fluorouracil derivatives of the present invention are known to have potent antitumor activity and can be utilized as antitumor agents for humans and animals, and they are particularly useful in treatment of or prophylaxis of metastases of malignant tumors such as uterine cancer, esophagus carcinoma, cutaneous cancer, gastric cancer, lung cancer, liver cancer, colic and rectum cancer, pancreas cancer, mammary cancer, bladder cancer, trophoblastic neoplasia, cerebral tumor, lymphosarcoma, leukemia, and the like [Japanese Unexamined Patent Publication Nos. 57-16881 and 57-67578].
In the prior art, the 5-fluorouracil derivatives have been prepared in the following ways.
(1) Reaction of 5-FU with 3-halophthalide in the presence of an organic or inorganic base [Japanese Unexamined Patent Publication No. 57-16881]. PA0 (2) Reaction of 5-FU with 3-trifluoroacetylphthalide [Japanese Patent Application No. 57-181047]. PA0 N,N,N-triethyl-3-oxo-1,3-dihydro-1-isobenzofuranylammonium bromide, PA0 N,N,N-triethyl-3-oxo-1,3-dihydro-1-isobenzofuranylammonium chloride, PA0 4-Methyl-4-(3-oxo-1,3-dihydro-1-isobenzofuranyl)-morpholinium bromide, PA0 4-Methyl-4-(3-oxo-1,3-dihydro-1-isobenzofuranyl)-morpholinium chloride, PA0 4-Ethyl-4-(3-oxo-1,3-dihydro-1-isobenzofuranyl)-morpholinium bromide. PA0 1-(3-Oxo-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-6-trimethylsilyloxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-6-triethylsilyloxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-6-t-butyldimethylsilyloxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorou racil, PA0 1-(3-Oxo-6-t-butyldiethylsilyloxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorour acil, PA0 1-(3-Oxo-6-methoxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-6-ethoxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-6-nitro-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-6-cyano-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-6-carboxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-6-methoxycarbonyl-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-6-ethoxycarbonyl-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-4-trimethylsilyloxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-4-t-butyldimethylsilyloxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorou racil, PA0 1-(3-Oxo-4-methoxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-4-ethoxy-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-4-nitro-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-4-cyano-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-4-carbonyl-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-4-methoxycarbonyl-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil, PA0 1-(3-Oxo-4-ethoxycarbonyl-1,3-dihydro-1-isobenzofuranyl)-5-fluorouracil.